Whether an initial triggering of the immune system by antigen becomes defective with aging is being explored in this project. Initial studies are focused on the liver since this tissue was found in previous studies to be a major site of antigen metabolism for soluble 3H-aniline-azo-bovine serum albumin (3H-BSA), injected intravenously and without adjuvant. Results from an extensive study in Sprague-Dawley rats are a model for antigen studies recently begun in Fischer-344 rats (NIA colony) of age 2, 6, 12 and 24 months. Pure populations of hepatocytes, isolated from immunized rats, have provided a secondary challenge to antigen-primed rats as assayed by the Farr technique and specifically inhibited by antigen. The antigen in hepatocytes is associated with RNA obtained from phenol-chloroform extraction of magnesium-precipitated polysomes. Polysome-associated antigen, proven to be a direct consequence of in vivo antigenic stimulation, has been characterized by sucrose density gradient centrifugation, RNA extraction and gel electrophoresis, and is capable of transferring both a primary and a secondary humoral immune response. Non-parenchymal liver cells and polysomes from spleen, lymph nodes, thymus, lungs and kidneys are being similarly characterized for antigen. Changes in in vivo antigen that seem correlated with aging will be the basis for further antigen transfer studies in this investigation, overall aimed at understanding why aging leads to an increased susceptibility to disease.